Trang Phan

ABSTRACT The position of nitrogen atoms in poly(4-vinylpyridine) (P4VP), compared to their poly(2-vinylpyridine) (P2VP) isomers, explains most difficulties faced when determining their molecular weight parameters by size exclusion chromatography, due to oligomers strongly adsorbing onto stationary phases. The high accessibility of these nitrogen atoms is shown here to be challenging also in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), probably accounting for the lack of mass data reported for P4VP in the literature. Using a “bottom-up” strategy starting from small oligomers prior to consider high molecular weight polymers, P4VP species were observed here to strongly interact with acidic matrix molecules such as 2,5-DHB when preparing MALDI sample using the traditional dried-droplet procedure. In contrast, MALDI best performed when using a solvent-free sample preparation involving a non-acidic matrix such as DCTB. Accordingly, reliable MS determination of molecular weight parameters could be achieved for P4VP up to about 40 kDa, as validated by diffusion NMR experiments.

ABSTRACT High-field dynamic nuclear polarization (DNP) may enhance the sensitivity of solid-state NMR experiments on a wide range of systems, including synthetic polymers, owing to the transfer of electron spin polarization from radicals to nuclei upon microwave irradiation (usually at cryogenic temperatures). Provided that the radicals are homogeneously dispersed in the sample, a uniform DNP enhancement is expected for all the signals in the C-13 cross-polarization magic angle spinning (CPMAS) spectrum. Here, we show that, in the case of methyl group containing polymers, a change in the cross-polarization (CP) dynamics induced by the moderate increase in sample temperature due to microwave irradiation may lead to the observation of apparent nonuniform enhancements in the DNP-enhanced C-13 CPMAS spectra. This peculiar behavior should be accounted for when measuring C-13 CP DNP enhancements on polymer materials, especially for heterogeneous polymer samples (for which truly nonuniform DNP enhancements could potentially be detected), or when quantitative results are sought.

ABSTRACT The benefits of the conformal coating of polyethylene oxide (PEO)-based polymer electrolyte by the electropolymerization technique on titania nanotubes (TiO2nts) are highlighted. Due to the presence of polymer electrolyte coating the nanotubes, the capacity of the half cell is improved by 45% at 1 C compared to bare TiO2nts. The polymer-coated TiO2nts in the full cell deliver an average capacity of ∼30 μA h cm-2 (120 mA h g-1) with LiNi0.5M1.5O4, ∼25 μA h cm-2 (100 mA h g-1) with LiFePO4 and ∼23 μA h cm-2 (90 mA h g-1) with LiCoO2, respectively during 50 cycles.

ABSTRACT This work compares the overall sensitivity enhancements provided by dynamic nuclear polarization (DNP) for the solid-state NMR characterization of polymer samples doped with biradicals and prepared either by film casting (FC), or by glass forming (GF) using 1,1,2,2-tetrachloroethane as the solvent. Analysis of amorphous and semicrystalline polymers (polystyrene, poly(ethylene oxide), polylactide, poly(methyl methacrylate)) of varying molecular weights showed that GF provided larger sensitivity enhancements than FC but yielded DNP-enhanced 13C CPMAS spectra of lower resolution for semicrystalline polymers, owing to line-broadening due to conformational distribution of the polymer chains in frozen solution. Moreover, use of deuterated solvents significantly reduced the intensity of the solvent signals in the DNP-enhanced 13C CPMAS spectra of polymers prepared by GF, while preserving the sensitivity enhancement observed for the polymer signals. For the polymers investigated here, both FC and GF performed better than incipient wetness impregnation, yielding overall sensitivity enhancements between 5 and 40.

ABSTRACT A series of anionic poly(ionic liquid)s with 1,2,3-triazolium counter cations are prepared by cation exchange between tailormade 1,3,4-trialkylated-1,2,3-triazolium iodides and a polystyrene derivative having pendant potassium bis-(trifluoromethylsulfonyl)imide groups. The physical and ion-conducting properties of the resulting materials are compared to the parent potassium-containing polyelectrolyte based on H-1 NMR, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and broadband dielectric spectroscopy (BDS) measurements. Substitution of the potassium counter cation by 1,2,3-triazolium charge carriers affords polyelectrolytes with improved processability (broader solubility and removal of the crystalline behavior) as well as a substantial increase in anhydrous ionic conductivity.

ABSTRACT Dynamic nuclear polarization (DNP) is shown to greatly improve the solid-state nuclear magnetic resonance (SSNMR) analysis of synthetic polymers by allowing structural assignment of intrinsically diluted NMR signals, which are typically not detected in conventional SSNMR. Specifically, SSNMR and DNP SSNMR were comparatively used to study functional polymers for which precise structural elucidation of chain ends is essential to control their reactivity and to eventually obtain advanced polymeric materials of complex architecture. Results show that the polymer chain-end signals, while hardly observable in conventional SSNMR, could be clearly identified in the DNP SSNMR spectrum owing to the increase in sensitivity afforded by the DNP setup (a factor similar to 10 was achieved here), hence providing access to detailed structural characterization within realistic experimental times. This sizable gain in sensitivity opens new avenues for the characterization of "smart" functional polymeric materials and new analytical perspectives in polymer science.

Coupling of liquid chromatography at critical conditions (LCCC) with on-line mass spectrometry (MS) detection was implemented via an electrospray ionization (ESI) interface, using a mobile phase containing the cationizing agent. Critical conditions established for poly(ethylene oxide) were used to characterize a poly(ethylene oxide)/polystyrene block copolymer (PEO-b-PS) in both MS and MS/MS modes. As co-oligomer molecules were successfully separated according to the PS block size, structural information could be reached from simplified MS spectra. The microstructure of this copolymer, synthesized by nitroxide-mediated polymerization, could further be unambiguously characterized in LCCC/ESI-MS/MS experiments since the PS block size could be reached by both the co-oligomer chromatographic behavior and its MS/MS pattern.

The interaction of estrogen receptor α (ERα) with the consensus LXXLL motifs of transcriptional coactivators provides an entry for functional ERα inhibition. Here, synthetic cell-permeable LXXLL peptide probes are brought forward that allow evaluation of the interaction of specific recognition motifs with ERα in the context of the cell. The probes feature a nona-arginine tag that facilitates cellular entry and induces probe localization in nucleoli. The nucleoli localization provides an explicit tool for evaluating the LXXLL motif interaction with ERα. The probes compete with coactivators, bind ERα, and recruit it into the nucleoli. The physical inhibition of the ERα-coactivator interaction by the probes is shown to be correlated with the inhibition of ERα-mediated gene transcription. This chemical biology approach allows evaluating the ERα-coactivator interaction and inhibitor binding directly in cells.

The Estrogen Receptors ERα and ERβ bind cofactor proteins via short LXXLL motifs. The exact regulation and selectivity of these interactions remains an open question and the role of post-translational modifications (PTMs) is virtually unexplored. Here, we designed an X(7)-LXXLL-X(7) T7 phage display library and screened this against four ER protein constructs: the 'naked' ERα and ERβ Ligand Binding Domains (LBDs) and the tyrosine phosphorylated ERα (pY537) and ERβ (pY488) LBDs. The site-selective tyrosine phosphorylated protein constructs were obtained via a protein semi-synthesis approach. Phage display screening yielded preferential sets of peptides. LXXLL peptides with a low pI/acidic C-terminus prefer binding to the naked ERβ over the phosphorylated ERβ analogue and ERα constructs. Peptides with a high pI/basic C-terminus show the opposite behaviour. These findings not only show regulation of the ERβ-cofactor interaction via tyrosine phosphorylation, but also suggest that ERβ and its tyrosine 488 phosphorylation play crucial roles in modulating interactions of coactivators to ERα since the natural Steroid Receptor Coactivators (SRCs) feature LXXLL motifs with acidic C-termini, while the repressor protein RIP140 features LXXLL motifs with basic C-termini. This insight provides explanation for ER transcriptional activity and can lead to more focussed targeting of the ER-coactivator interaction.

ABSTRACT Separation of functional poly(ethylene oxide) PEO and PEO block copolymers was investigated using liquid chromatography under critical conditions (LCCC) with a mixture of organic solvents as eluent. The optimum eluent is a mixture of 58.05% chloroform, 6.45% methanol, and 35.50% n-heptane (v/v/v) using a reverse phase (C8) column. Unlike what was expected, the elution mechanism is governed by the interaction of a polar end-group with the column. In these conditions, poly(ethylene oxide) (PEO) functionalized with either an acrylate or alkoxyamine moieties were separated. This allows us to investigate the efficiency of the synthesis of poly(ethylene oxide)-b-polystyrene (PEO-b-PS) and polystyrene-b-poly(ethylene oxide) b-polystyrene (PS-b-PEO-b-PS) block copolymers prepared via the combination of 1,2 radical intermolecular addition followed by the nitroxide-mediated polymerization NMP of styrene. Amphiphilic diblock PEO-b-PS and triblock PS-b-PEO-b-PS copolymers were also separated from PEO homopolymers using the same experimental conditions. We showed that the PEO block is then invisible, and the calibration curve obtained using PS homopolymer standards could be used to determine the whole molar mass of the PS block in block copolymers with PS and PEO segments, with a weak influence of the architecture.

Abstract Center for Education and Research on Macromolecules (CERM). Politique Scientifique Fédérale (Belgique)= Belgian Federal Science Policy. Fonds de la Recherche Scientifique (Communauté française de Belgique)-FNRS. Arkema. the French" CNRS"

Methyl methacrylate (MMA)/N, N-dimethyl acrylamide (DMA) gradient copolymers with various chemical composition were synthesized by nitroxide-mediated controlled radical polymerization (NMP). Molecular weight (MW) characterization via gel permeation ...

... Correspondence: Sylvain RA Marque, Aix-Marseille Universités, UMR-6517, case 521, Avenue Escadrille Normandie, Niemen 13397, Marseille, Cedex 20, France. Publication History. ... S. Marque, R. Martschke, M. Popov, H. Fischer, J. Chem. Soc., Perkin Trans. 2 1998, 1553. ...

Block copolymers constitute a fascinating class of polymeric materials which gives, both in solution and in the bulk, a rich variety of microstructures that are used in a broad range of applications, from advanced nanomaterials to biocompatible drug delivery systems.1, 2 ...

Discoidin domain-containing receptors (DDRs) exhibit a unique mechanism of action among the receptor tyrosine kinases (RTKs) because their catalytic activity is induced by extracellular collagen binding. Moreover, they are essential components in the assimilation of extracellular signals. Recently, DDRs were reported to be significantly linked to tumor progression in breast cancer by facilitating the processes of invasion, migration, and metastasis. Here, we report the successful development of a fluorescence-based, direct binding assay for the detection of type II and III DFG-out binders for DDR2. Using sequence alignments and homology modeling, we designed a DDR2 construct appropriate for fluorescent labeling. Successful assay development was validated by sensitive detection of a reference DFG-out binder. Subsequent downscaling led to convenient application to high-throughput screening formats. Screening of a representative compound library identified high-affinity DDR2 ligands validated by orthogonal activity-based assays, and a subset of identified compounds was further investigated with respect to DDR1 inhibition.

Different mRNA stabilizing elements including the 3'-stem-loop, the ribosome binding sites (RBS), the 5'-stem-loop and the spacer region between the RBS and the 5'-stem-loop were analysed in detail to increase mRNA stability resulting in enhanced expression of heterologous proteins. In addition, in combination with mRNA stabilizing elements, we propose a new class of…

Miniprotein phage display screening yields structured peptides with high affinity for the Estrogen Receptor (ER). Hits from apamin phage libraries feature a LXXLL motif specifically placed on the predefined miniprotein helical segment. The apamin scaffold also allows optimization of flanking amino acids to ensure an optimal ER binding affinity.

ABSTRACT Molecular organization of MALDI samples is suspected to play a major role in the ionization process. Using solvent-free conditions to prepare polymer samples to be mass analyzed, we show here that the grinding time influenced not only the quality of MALDI data but also the nature of detected adducts. In this context, molecular organization of these MALDI samples was studied by solid-state NMR, due to the ability of this technique to reveal changes in the local nuclear environment in solids. The model system investigated here was composed of 2,5-DHB as the matrix, a small poly(ethylene oxide) (PEG) as the analyte and cesium chloride as the cationizing agent, allowing H-1, C-13 and Cs-133 sites to be directly probed using NMR. To ensure reproducible data, the vortex method was chosen to grind the sample components in the solid state. Three different phases within the MALDI samples were evidenced through NMR. After grinding the three sample components for short times (ca. 2 min), the solid was composed of two phases, a crystalline 2,5-DHB phase and a matrix-PEG co-crystal. In spite of the addition of a cesium salt in the ternary mixture, laser irradiation of these samples only produced polymer sodium adducts. In contrast, longer grinding times (ca. 16 min), shown to promote the formation of a third phase composed of a matrix-salt co-crystal, allowed optimal production of PEG cesium adducts. Water molecules were evidenced for the first time to be part of the MALDI sample. Water could only be observed in the 2,5-DHB-CsCl crystalline complex and its presence in the grinding atmosphere was shown to be necessary for this complex to form. The variety of structural information obtained by solid-state NMR on the investigated model sample showed how this technique can be successfully employed to gain new insights into the MALDI mechanism

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) is the technique of choice to achieve molecular weight data for synthetic polymers. Because the success of a MALDI-MS analysis critically depends on a proper matrix and cation selection, which in turn relates closely to the polymer chemical nature and size, prior estimation of the polymer size range strongly helps in rationalizing MALDI sample preparation. We recently showed how pulsed gradient spin echo (PGSE) nuclear magnetic resonance could be used as an advantageous alternative to size exclusion chromatography, to rationalize MALDI sample preparation and confidently interpret MALDI mass spectra for homopolymers. Our aim here is to extend this methodology to the demanding case of amphiphilic block copolymers, for which obtaining prior estimates on the Mw values appears as an even more stringent prerequisite. Specifically, by studying poly(ethylene oxide) polystyrene block copolymers of distinct molecular weights and relative block weight fractions, we show how PGSE data can be used to derive the block Mw values. In contrast to homopolymers, such determination requires not only properly recorded calibration curves for each of the polymers constituting the block copolymers but also an appropriate hydrodynamic model to correctly interpret the diffusion data.